Koletzko Sibylle, Lee Hye-Seung, Beyerlein Andreas, Aronsson Carin A, Hummel Michael, Liu Edwin, Simell Ville, Kurppa Kalle, Lernmark Åke, Hagopian William, Rewers Marian, She Jin-Xiong, Simell Olli, Toppari Jorma, Ziegler Anette-G, Krischer Jeffrey, Agardh Daniel
*Dr. v. Hauner Children's Hospital, University Munich Medical Center, Munich, Germany †Health Informatics Institute, Department of Paediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, USA ‡Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany §Department of Clinical Sciences, Lund University, Skane University Hosptial, Malmo, Sweden ||Digestive Health Institute, University of Colorado, Children's Hospital Colorado, Aurora, CO, USA ¶Medicity Laboratory, University of Turku, Turku, Finland #Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland **Pacific Northwest Diabetes Research Institute, Seattle WA, USA ††Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora CO, USA ‡‡Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta GA, USA §§Department of Paediatrics, Turku University Hospital, Turku, Finland ||||Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland ¶¶Departments of Physiology, University of Turku, Turku, Finland.
J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):417-424. doi: 10.1097/MPG.0000000000001682.
Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort.
From 2004 to 2010, infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models.
Of 6087 analyzed singletons, 1600 (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR] = 0.85; 95% confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75; 95% CI 0.58, 0.98; P = 0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education, and breast-feeding duration, significance was lost for CDA (HR = 0.91; 95% CI 0.78, 1.06; P = 0.20) and CD (HR = 0.85; 95% CI 0.65, 1.11; P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development.
C-section is not associated with increased risk for CDA or CD in the offspring.
剖宫产与后代的多种免疫介导疾病相关。我们在一个跨国出生队列中研究了分娩方式与乳糜泻(CD)及乳糜泻自身免疫(CDA)之间的关系。
2004年至2010年,对普通人群中人类白细胞抗原(HLA)DR3-DQ2或DR4-DQ8检测呈阳性的婴儿进行了青少年糖尿病环境决定因素(TEDDY)研究。每年对儿童进行转谷氨酰胺酶自身抗体筛查,若呈阳性,则在3至6个月后重新检测,持续呈阳性者定义为CDA。通过Fisher精确检验或Wilcoxon秩和检验研究剖宫产与母亲特征(年龄、教育水平、产次、孕前体重、糖尿病、吸烟、孕期体重增加)及儿童特征(胎龄、出生体重)之间的关联。通过Cox比例风险回归模型计算CDA或CD的风险比(HR)。
在6087例分析的单胎中,1600例(26%)通过剖宫产出生(德国38%,美国37%,芬兰18%,瑞典16%),其余为无器械辅助的阴道分娩;979例(16%)发生了CDA,343例(6%)发生了CD。剖宫产与较低的CDA风险(风险比[HR]=0.85;95%置信区间[CI]0.73,0.99;P=0.032)和CD风险(HR=0.75;95%CI0.58,0.98;P=0.034)相关。在调整国家、性别、HLA基因型、家族性CD、母亲教育程度和母乳喂养持续时间后,CDA(HR=0.91;95%CI0.78,1.06;P=0.20)和CD(HR=0.85;95%CI0.65,1.11;P=0.24)的相关性消失。术前胎膜破裂对CDA或CD的发生没有影响。
剖宫产与后代CDA或CD的风险增加无关。